Chronic fatigue syndrome (CFS), fibromyalgia (FM), Gulf War Illness (GWI) and related chronic illnesses have been considered diagnoses of exclusion where no other diagnosis fits well. CFS has been defined by specific requirements of fatigue, its duration, associated symptoms, and initial clinical and laboratory evaluation. There has existed no reliable laboratory means for determining whether an individual was suffering from CFS, FM, or some other disease. Gulf War illness and CFS share many clinical characteristics and may be variations of similar underlying pathophysiology. Accordingly, a felt need for a method of testing for CFS, FM, and related illnesses, such as GWI, existed. We have previously demonstrated low level activation of coagulation in many of these patients by measurement of blood levels of fibrinogen, prothrombin fragment 1+2, thrombin-antithrombin complexes, soluble fibrin monomer, and platelet CD62P activation. We have now conducted analyses of underlying genetic and metabolic factors that could contribute to a predisposition to develop such illnesses or yield a more enhanced activation of coagulation in patients who acquire the illnesses. These new tests include Protein C, Protein S, antithrombin, activated protein C resistance, prothrombin activity, plasminogen activator inhibitor-1, lipoprotein (a) and homocysteine. Various methods including protein, enzymatic activity, amino acid analysis and analysis of gene sequences apply to these genetic and metabolic procoagulant markers.